rhIL-12 as adjuvant augments lung cell cytokine responses to pneumococcal whole cell antigen.

Abstract

Conjugate pneumococcal vaccines offer suboptimal protection against mucosal infections and are restricted in serotype and geographical coverage. New protein-based vaccines using conserved pneumococcal antigens and better mucosal adjuvant technology are urgently needed. Interleukin-12 (IL-12) has shown efficacy as a pneumococcal protein vaccine adjuvant in murine models of pneumococcal infection. Systemic administration of recombinant human (rh) IL-12 to humans, however, has been associated with adverse clinical and laboratory side effects. Inhaled forms of IL-12 have improved the safety profiles in humans, as suggested by animal models. Here we evaluated rhIL-12 as an adjuvant on ex vivo human BAL cells when stimulated with pneumococcal whole cells. We show that co-incubation of ex vivo human BAL cells with pneumococcal whole cell antigen (WCA) and a low dose of rhIL-12 (2 ng) can elevate TNF production compared to treatment with WCA (p=0.06) or rhIL-12 (p=0.03) alone. The production of IFNγ was also increased but not in an antigen specific manner, suggesting perhaps a predominant Th(1) response. Our data suggest that 100-200-fold lower doses of inhaled rhIL-12 than those previously tested for systemic use may be adequate in a phase 1 study and commend further evaluation of rhIL-12 as a potential mucosal adjuvant in human vaccine studies.

• Authors: Adam K A Wright, Ioanna Christopoulou, Sherouk El Batrawy, Jane Limer, Stephen B Gordon
• Journal: Immunobiology (Immunobiology) Vol. 216 Issue 10 Pg. 1143-7 (Oct 2011) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 21601939 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier GmbH. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Antigens, Bacterial
• Cytokines
• Recombinant Proteins
• Interleukin-12

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antigens, Bacterial (administration & dosage, immunology)
• Bronchoalveolar Lavage Fluid (cytology)
• Cytokines (biosynthesis)
• Humans
• Interleukin-12 (administration & dosage)
• Leukocytes, Mononuclear (drug effects, immunology)
• Lung (cytology, immunology)
• Mice
• Recombinant Proteins (administration & dosage)
• Streptococcus pneumoniae (immunology)